NM_002734.5(PRKAR1A):c.754A>G (p.Lys252Glu) AND Carney complex, type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 9, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001064627.8

Allele description [Variation Report for NM_002734.5(PRKAR1A):c.754A>G (p.Lys252Glu)]

NM_002734.5(PRKAR1A):c.754A>G (p.Lys252Glu)

Gene:

PRKAR1A:protein kinase cAMP-dependent type I regulatory subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q24.2

Genomic location:

Preferred name:

NM_002734.5(PRKAR1A):c.754A>G (p.Lys252Glu)

HGVS:

NC_000017.11:g.68527885A>G
NG_007093.3:g.119263A>G
NM_001276289.2:c.754A>G
NM_001276290.1:c.754A>G
NM_001278433.2:c.754A>G
NM_001369389.1:c.754A>G
NM_001369390.1:c.754A>G
NM_002734.5:c.754A>GMANE SELECT
NM_212471.3:c.754A>G
NM_212472.2:c.754A>G
NP_001263218.1:p.Lys252Glu
NP_001263219.1:p.Lys252Glu
NP_001265362.1:p.Lys252Glu
NP_001356318.1:p.Lys252Glu
NP_001356319.1:p.Lys252Glu
NP_002725.1:p.Lys252Glu
NP_997636.1:p.Lys252Glu
NP_997637.1:p.Lys252Glu
LRG_514t1:c.754A>G
LRG_514t2:c.754A>G
LRG_514:g.119263A>G
LRG_514p2:p.Lys252Glu
NC_000017.10:g.66524026A>G
NM_002734.4:c.754A>G

Protein change:

K252E

Links:

dbSNP: rs763921895

NCBI 1000 Genomes Browser:

rs763921895

Molecular consequence:

NM_001276289.2:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276290.1:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278433.2:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369389.1:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369390.1:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002734.5:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_212471.3:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_212472.2:c.754A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Carney complex, type 1 (CNC1)
Synonyms:: CARNEY MYXOMA-ENDOCRINE COMPLEX
Identifiers:: MONDO: MONDO:0008057; MedGen: C2607929; Orphanet: 1359; OMIM: 160980

Recent activity

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RecName: Full=Nanos homolog 1; Short=NOS-1; AltName: Full=EC_Rep1a
RecName: Full=Nanos homolog 1; Short=NOS-1; AltName: Full=EC_Rep1a
gi|41688589|sp|Q8WY41.2|NANO1_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229537	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 9, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001229537

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 9, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001229537.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRKAR1A-related conditions. This variant is present in population databases (rs763921895, ExAC 0.002%). This sequence change replaces lysine with glutamic acid at codon 252 of the PRKAR1A protein (p.Lys252Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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